The present invention relates generally to vaccines, the treatment of viruses, and the purification of compounds useful for the same. More specifically, the present invention relates to the use and preparation of low molecular weight factors having anti-viral properties.
Gyles et al., 47 Poultry Sci. 430 (1968), and Gyles and Brown, 50 Poultry Sci. 901 (1971), likewise reported that regression of Rous sarcoma virus (RSV)-induced tumors is under genetic control in chickens. Further, Schierman et al., 5 Immunogenetics 325 (1977), and Collins et al., 5 Immunogenetics 333 (1977), have identified a single dominantly inherited gene, designated R-Rs-1, located outside the B blood locus, which appears to be the primary genetic factor regulating regression in chickens.
Differences between the regressor and progressor chickens in early recognition and speed and intensity of response by their immunological systems may be an important key to regression. Gyles et al., 46 Poultry Sci. 465 (1967), found that the time required for a tumor to be initiated from wing-web inoculation of RSV varied among genetic lines and among individuals within a genetic line. Gyles et al., 56 Poultry Sci. 758 (1977), discovered that the immune response to a secondary RSV challenge with either RSV or Rous sarcoma tumor homogenate (RSTH) in the opposite wing-web was met by an earlier immune response in the regressor line (R-line) than in the progressor line (Pr-line), but that both lines could mount a response to the second challenge.
Our search for a low molecular weight factor (LMF) present in chicken sera that may exhibit viral-neutralizing or anti-tumor activity was stimulated by the discoveries of Burzynski et al., 9 Physiol. Chem. Phys. 485 (1977). They have isolated and identified a class of peptides present in sera and urine of normal patients that are potent inhibitors of some human neoplasms. See also Beall et al., 3 Cancer Biochem. Biophys. 93 (1979).
As reported by Whitfill et al., 61 Poultry Sci. 1573 (1982), a low molecular weight fraction (less than 5000 daltons) was isolated by gel permeation chromatography from chicken sera. This fraction possessed virus-neutralizing capacity and appeared to be present at high levels in regressor chicken hyperimmune sera, a sera obtained from regressor chickens that had fully regressed Rous sarcomas and had also received a secondary booster inoculation of Rous sarcoma tumor homogenate before the blood was removed by cardiac puncture. However, high levels of activity was not found in regressor chicken sera obtained before initial RSV challenge or 32 days after challenge when the tumors completely regressed. Both the regressor and progressor chickens respond to the viral challenge by developing tumors, but the Rous virus elicits a more rapid and intense anti-tumor response in regressor chickens. The active low molecular weight fraction is called the low molecular weight viral neutralizing factor (LMF).
Whitfill, "Time Course of Production of Low Molecular Weight Viral-Neutralizing Substance(s) in Chickens," 17 Springer/Immunogenetics 387 (1983), discusses how low molecular weight neutralizing factors can be isolated from blood of the regressor line chickens.
Gyles and Whitfill, Annual Report of Project Contributions to NE-60 (October 1986), report that LMF neutralized Rous sarcoma virus when administered in combination therewith to nine day old SPAFAS egg embryos as measured by chorioallantoic membrane pock formation. The present application is based upon our continuing investigation into the activity of LMF.
Gyles and Whitfill, Annual Report of Project Contributions to NE-60 (October 1987) report that LMF also has antiviral activity against Infectious Bursal Disease Virus and Infectious Bronchitis Virus.